Snake venom metalloproteinases: structure/function relationships studies using monoclonal antibodies

Autor(es)

Tanjoni, Isabelle ^[1] ; Butera, Diego ; Bento, Luciana ; Della-Casa, Maisa S. ; Marques-Porto, Rafael ; Takehara, Harumi A. ; Gutiérrez, Jose M. ; Fernandes, Irene ; Moura-da-Silva, Ana M. ^[9]

Afiliação do(s) autor(es)

^[1] São Paulo (Estado). Secretaria de Estado da Saúde. Instituto Butantan - Brasil

^[9] São Paulo (Estado). Secretaria de Estado da Saúde. Instituto Butantan - Brasil

• Tipo de documento: Artigo Científico
• Fonte: Toxicon; v. 42, n. 7, p. 801-808, Dec. 2003.
• Área do conhecimento: Ciências Biológicas - Farmacologia
• Assunto(s): Farmacologia molecular Venenos de origem animal Serpentes Bothrops jararaca Anticorpos monoclonais Metaloproteinases Desintegrinas

Resumo

Snake Venom Metalloproteinases (SVMPs) are synthesized as zymogens and undergo proteolytic processing resulting in a variety of multifunctional proteins. Jararhagin is a P-III SVMP, isolated from the venom of Bothrops jararaca, comprising metalloproteinase, disintegrin-like and cysteine-rich domains. The catalytic domain is responsible for the hemorrhagic activity. The disintegrin-like/cysteine-rich domains block alpha-2-beta-1 integrin binding to collagen and apparently enhance the hemorrhagic activity of SVMPs. The relevance of disintegrin-like domain is described in this paper using a series of mouse anti-jararhagin monoclonal antibodies (MAJar 1-7). MAJar 3 was the only antibody able to completely neutralize jararhagin hemorrhagic activity. Neutralization of catalytic activity was partial by incubation with MAJar 1. MAJars 1 and 3 efficiently neutralized jararhagin binding to collagen with IC50 of 330 and 8.4 nM, respectively. MAJars 1 and 3 recognized the C-terminal portion of the disintegrin domain, which is apparently in conformational proximity with the catalytic domain according to additivity tests. These data suggest that disintegrin-like domain epitopes are in close contact with catalytic site or functionally modulate the expression of hemorrhagic activity in SVMPs. (AU)

• Processo FAPESP: 00/13651-0 - Obtenção de disintegrinas nativas e recombinantes de venenos viperídeos: importantes ferramentas para o estudo de adesão celular
• Beneficiário: Ana Maria Moura da Silva
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 99/12432-3 - Obtencao e caracterizacao de anticorpos monoclonais anti-jararagina.
• Beneficiário: Isabelle Tanjoni
• Modalidade de apoio: Bolsas no Brasil - Mestrado